Association of Clopidogrel Treatment With Risk of Mortality and Cardiovascular Events Following Myocardial Infarction in Patients With and Without Diabetes

Study Questions:

What is the clinical effectiveness associated with clopidogrel treatment after myocardial infarction (MI) in patients with diabetes?


By individual-level linkage of the Danish nationwide administrative registries between 2002-2009, patients who were hospitalized with incident MI and who had survived and not undergone coronary artery bypass surgery 30 days after discharge were followed up for as long as 1 year (maximally until December 31, 2009). Adjusted for age, sex, comorbidity, calendar year, concomitant pharmacotherapy, and invasive interventions, hazard ratios that were associated with clopidogrel in patients with and without diabetes were analyzed by Cox proportional-hazard models and propensity score-matched models. The main outcome measures were all-cause mortality, cardiovascular mortality, and a composite endpoint of recurrent MI and all-cause mortality.


Of the 58,851 patients included in the study, 7,247 (12%) had diabetes and 35,380 (60%) received clopidogrel. In total, 1,790 patients (25%) with diabetes and 7,931 patients (15%) without diabetes met the composite endpoint. Of these, 1,225 (17%) with and 5,377 (10%) without diabetes died. In total, 978 patients (80%) with and 4,100 patients (76%) without diabetes died of events of cardiovascular origin. For patients with diabetes who were treated with clopidogrel, the unadjusted mortality rates (events/100 person-years) were 13.4 (95% confidence interval [CI], 12.8-14.0) versus 29.3 (95% CI, 28.3-30.4) for those not treated. For patients without diabetes who were treated with clopidogrel, the unadjusted mortality rates were 6.4 (95% CI, 6.3-6.6) versus 21.3 (95% CI, 21.0-21.7) for those not treated. However, among patients with diabetes versus those without diabetes, clopidogrel was associated with less effectiveness for all-cause mortality (hazard ratio [HR], 0.89; 95% CI, 0.79-1.00 vs. HR, 0.75; 95% CI, 0.70-0.80; p for interaction = 0.001) and for cardiovascular mortality (HR, 0.93; 95% CI, 0.81-1.06 vs. HR, 0.77; 95% CI, 0.72-0.83; p for interaction = 0.01), but not for the composite endpoint (HR, 1.00; 95% CI, 0.91-1.10 vs. HR, 0.91; 95% CI, 0.87-0.96; p for interaction = 0.08). Propensity score-matched models gave similar results.


The authors concluded that among patients with diabetes compared with patients without diabetes, the use of conventional clopidogrel treatment after MI was associated with lower reduction in the risk of all-cause death and cardiovascular death.


The current study reports a reduced 1-year clinical effectiveness associated with clopidogrel treatment in patients with diabetes, and supports previous knowledge of platelets in diabetes showing high platelet reactivity and diminished responsiveness to standard clopidogrel treatment. While these findings raise the possibility that patients with diabetes may benefit from more potent platelet inhibitor strategies, prospective clinical studies with hard clinical endpoints are indicated to prove such a hypothesis. Because of the relatively higher absolute risks found in patients with diabetes, use of clopidogrel still translates into a significant reduction in event rates for patients with diabetes.

Keywords: Cause of Death, Outcome Assessment, Health Care, Incidence, Myocardial Infarction, Platelet Aggregation Inhibitors, Cardiovascular Diseases, Blood Platelets, Coronary Artery Bypass, Diabetes Mellitus

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